Since the discovery of RNA interference (RNAi), first in plants in 1990 and then in animals in 1998, this pathway has generated significant interest for its utility in biological studies as well as in drug development. As part of the RNAi pathway, small interfering RNAs (siRNAs) induce post-transcriptional gene silencing in a sequence-specific manner utilizing endogenous cellular machinery, in essence suppressing protein synthesis and thus effectively inhibiting protein function. This technology is used routinely as a research tool for target validation, biological pathway analysis, and imaging of biological systems. In addition, the ubiquity of the RNAi pathway within the body and the ease with which the target of interest can be altered have made siRNA an attractive class of molecules for the treatment of cancer, viral and bacterial infections, neurodegenerative diseases, and genetic disorders. In addition, RNAi therapies are of interest to enhance the effectiveness of existing therapies; for example, RNAi could be used to target multidrug resistance genes to re-sensitize cancer cells to traditional chemotherapy.
SiRNA is subject to rapid enzymatic degradation and has difficulty entering the cell due to its relatively large size and polyanionic polar nature that resists passage across the non-polar membrane of a cell. These difficulties suggest that delivery of siRNA into cells and tissue within the body is a challenge to the realization of siRNA for diagnostic, imaging and therapeutic use. Delivery systems that both prevent enzymatic degradation and effectively deliver siRNA across the cell membrane are of interest for the utility of biological siRNA tools and siRNA therapies to be realized.